α4β7 integrin expression is associated with the leukemic evolution of human and murine T-cell lymphoblastic lymphomas

Riccardo Dolcetti, Roberto Giardini, Claudio Doglioni, Roberta Cariati, Fabrizio Pomponi, Claudia D'Orazi, Stefania Rao, Andrew I. Lazarovits, Eugene C. Butcher, Mauro Boiocchi

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Abstract

We have previously shown that the in vivo coordinated expression of individual α4 and β7 integrin chains correlated with the leukemic potential displayed by cell lines derived from murine lymphoblastic T-cell lymphomas (T-LBLs) when transplanted subcutaneously into syngeneic AKR mice. In the present study, by using immunofluorescence and immunocytochemical analyses, we have confirmed that the in vive up-regulation of the α4β7 heterodimeric complex is associated with the leukemic behavior of AKR T- LBLs. In addition, when compared with the parental, highly leukemic NQ22 cells, the variant cell line NQ22V exhibited a reduced leukemic potential that was invariably associated with a delayed α4β7 up-regulation in vivo. Moreover, the leukemic cell line SJ-1, derived from a spontaneous T-LBL of the SJL strain, also displayed high levels of α4β7 expression with a pattern of tissue distribution similar to that of NQ22 cells from leukemic AKR animals. Of note, in most of the tissues involved by murine T-LBL dissemination, and particularly in liver, kidney, and lung, α4β7-positive leukemic cells were always located around strongly VCAM-1-positive vascular spaces. These findings are consistent with a possible role of α4β7/VCAM-1 interactions in the extravasation and, consequently, in the leukemic- dissemination of murine T-LBL cells. Immunocytochemical analysis carried out in 11 human T-LBLs showed that pathological lymph nodes from all 7 cases with bone marrow infiltration at presentation carried α4β7-positive cells, whereas all 4 aleukemic T-LBLs were repeatedly α4β7 negative, also in metachronous lesions. These findings suggest that α4β7-positive human T- LBLs may represent a distinct clinicopathological entity. In addition, α4β7 expression was significantly more prevalent in younger patients (

Original languageEnglish
Pages (from-to)1595-1605
Number of pages11
JournalAmerican Journal of Pathology
Volume150
Issue number5
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Dolcetti, R., Giardini, R., Doglioni, C., Cariati, R., Pomponi, F., D'Orazi, C., Rao, S., Lazarovits, A. I., Butcher, E. C., & Boiocchi, M. (1997). α4β7 integrin expression is associated with the leukemic evolution of human and murine T-cell lymphoblastic lymphomas. American Journal of Pathology, 150(5), 1595-1605.